A structure-activity-relationship study of angiotensin homologs and analogs will be performed in an attempt to determine the structural requirements for agonist and antagonist activities in the adrenal cortex. Cell suspensions of the capsular layer on the rabbit adrenal cortex will be used and aldosterone determined by radioimmunoassay. Pathways of biotransformation of angiotensin I, II, des-aspl-angiotensin I and II will be studied in vivo and in the isolated adrenal cells, perfused kidney and arteries. The effects of changes in sodium metabolism on biotransformation and sensitivity of the adrenal cortical cells to angiotensins will be studied. The mechanism of action in the adrenal cortex will be pursued. Studies will be carried out with the angiotensins, ACTH and K ions in cortical cell suspension determining changes in 3', 5'-cyclic AMP and/or activation of guanosyl cyclase. The effects of K ions will be studied plus/minus ouabain and intracellular potassium concentration correlated with steroidogenesis. The effects of ouabain on angiotensin-induced steroidogenesis will be studied and it will be determined if angiotensin produces an increase in intracellular potassium. The effects of des-aspl-angiotensin II will be compared to those of angiotensin II in stimulating adrenal mitochondrial conversion of H3-corticosterone to aldosterone.